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David R. Borchelt
Researcher at University of Florida
Publications - 267
Citations - 36854
David R. Borchelt is an academic researcher from University of Florida. The author has contributed to research in topics: SOD1 & Amyloid precursor protein. The author has an hindex of 87, co-authored 258 publications receiving 34660 citations. Previous affiliations of David R. Borchelt include University of California, San Francisco & University of Minnesota.
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Journal ArticleDOI
Familial Alzheimer's Disease–Linked Presenilin 1 Variants Elevate Aβ1–42/1–40 Ratio In Vitro and In Vivo
David R. Borchelt,Gopal Thinakaran,Christopher B. Eckman,Christopher B. Eckman,Michael K. Lee,Frances Davenport,Tamara Ratovitsky,Cristian Mihail Prada,Grace Kim,Sophia Seekins,Debra Yager,Hilda H. Slunt,Rong Wang,Mary Seeger,Allan I. Levey,Sam Gandy,Neal G. Copeland,Nancy A. Jenkins,Donald L. Price,Steven G. Younkin,Steven G. Younkin,Sangram S. Sisodia +21 more
TL;DR: These studies provide compelling support for the view that one mechanism by which these mutant PS1 cause AD is by increasing the extracellular concentration of Abeta peptides terminating at 42(43), species that foster Abeta deposition.
Journal ArticleDOI
APP processing and synaptic function.
Flavio Kamenetz,Taisuke Tomita,Helen Hsieh,Helen Hsieh,Guy R. Seabrook,David R. Borchelt,Takeshi Iwatsubo,Sangram S. Sisodia,Roberto Malinow,Roberto Malinow +9 more
TL;DR: It is shown that neuronal activity modulates the formation and secretion of Abeta peptides in hippocampal slice neurons that overexpress APP, and it is proposed that activity-dependent modulation of endogenous Abeta production may normally participate in a negative feedback that could keep neuronal hyperactivity in check.
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An adverse property of a familial ALS-linked SOD1 mutation causes motor neuron disease characterized by vacuolar degeneration of mitochondria
Philip C. Wong,Carlos A. Pardo,David R. Borchelt,Michael K. Lee,Neal G. Copeland,Nancy A. Jenkins,Sangram S. Sisodia,Don W. Cleveland,Don W. Cleveland,Donald L. Price +9 more
TL;DR: Mutations in Cu/Zn superoxide dismutase cause a subset of cases of familial amyotrophic lateral sclerosis, and four lines of mice accumulating one of these mutant proteins (G37R) develop severe, progressive motor neuron disease.
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ALS-Linked SOD1 Mutant G85R Mediates Damage to Astrocytes and Promotes Rapidly Progressive Disease with SOD1-Containing Inclusions
Lucie Bruijn,Mark W. Becher,Michael K. Lee,K. L. Anderson,Nancy A. Jenkins,Neal G. Copeland,Sangram S. Sisodia,Jeffrey D. Rothstein,David R. Borchelt,Donald L. Price,Don W. Cleveland +10 more
TL;DR: It is reported here that even low levels of another mutant, G85R, cause motor neuron disease characterized by an extremely rapid clinical progression, without changes in SOD1 activity.
Journal ArticleDOI
Mutant presenilins specifically elevate the levels of the 42 residue β-amyloid peptide in vivo: evidence for augmentation of a 42-specific γ secretase
Joanna L. Jankowsky,Joanna L. Jankowsky,Daniel J. Fadale,Jeffrey Anderson,Guilian Xu,Victoria Gonzales,Nancy A. Jenkins,Neal G. Copeland,Michael K. Lee,Linda H. Younkin,Steven L. Wagner,Steven G. Younkin,David R. Borchelt +12 more
TL;DR: A direct correlation between the concentration of Aβ42 and the rate of amyloid deposition is demonstrated and suggests that PS1 variants do not simply alter the preferred cleavage site for γ-secretase, but rather that they have more complex effects on the regulation of ιsecretase and its access to substrates.